Cognitive functioning in young and middle-aged unmedicated out-patients with major depression: testing the effort and cognitive speed hypotheses.

BACKGROUND: Cognitive deficits are common in major depressive disorder, but their nature is unclear. The effort hypothesis states that performance on effortful tasks is disproportionately impaired compared with the performance on automatic tasks. The cognitive speed hypothesis states that depression is characterized by cognitive slowness, which is a source of cognitive dysfunctioning. The present study investigated both theories in unmedicated adult depressive patients. It was also investigated whether the cognitive deficits can be attributed to more general physical illness-related factors or specifically to depressive disorder. METHOD: Thirty non-psychotic depressive out-patients were compared with 38 healthy control subjects and 25 patients with severe allergic rhinitis. The effects of group on more automatic and more effortful aspects of cognitive tasks measuring cognitive speed (Concept Shifting Task, Stroop Colour Word Test, Memory Scanning Test) and memory retrieval (Visual Verbal Learning Task, Verbal Fluency Test) were evaluated by MANCOVA. Age, sex, education and pre-morbid intelligence were treated as covariates. RESULTS: The depressive group had cognitive deficits in the automatic processing subtask of the Stroop, memory scanning and memory span. Performance on more effortful tasks was not impaired. CONCLUSIONS: Our results are more consistent with the cognitive speed hypothesis. Cognitive functioning in depressive disorder seems to be characterized by a reduced speed of information processing in automatic subtasks.

Salivary cortisol patterns and cognitive speed in major depression: a comparison with allergic rhinitis and healthy control subjects.

Few studies have investigated the relationship between cortisol and cognitive functions other than memory in depression. This study investigated daily salivary cortisol patterns (basal cortisol levels at 08:00, 16:00, and 21:00 h and flatness of the diurnal curve) in relation to cognitive speed and memory. Twenty-seven unmedicated outpatients with major depressive disorder (MDD) were compared with 36 healthy controls and with 20 allergic rhinitis patients, to determine whether effects should be ascribed to MDD or to more general disease-related processes. MDD patients were characterised by a flatter diurnal cortisol curve and by reduced cognitive speed. Flatter cortisol curves were associated with cognitive slowness. However, this relationship is unlikely to be causal; after control for depressive symptoms and group membership, flatness of the diurnal cortisol curve was no longer a significant predictor of cognitive slowness. Thus, MDD and related depressive symptoms appeared to be independently associated with altered cortisol secretory patterns and with decrements in cognitive speed.

Test-retest stability of the behavioural assessment of the dysexecutive syndrome in a sample of psychiatric patients.

The Behavioural Assessment of the Dysexecutive Syndrome (BADS) is a relatively new test battery designed to measure disorders of executive functions. We studied the temporal stability of the BADS in a sample of 22 adult psychiatric patients. All patients were administered the BADS twice with an interval of 3 weeks. Test-retest correlations for the BADS tests ranged from .22 to .85. On the repeat administration, patients obtained higher scores on one test as well as on the total BADS. Our results suggest that the BADS should not be administered on two occasions a few weeks apart.

[Consensus on the concepts of cortical, subcortical and frontal dementia. Research by national and international dementia experts]. / Consensus over de begrippen corticale, subcorticale en frontale dementie. Een onderzoek onder nationale en internationale dementie-experts.

The level of agreement concerning the concepts cortical, subcortical and frontal dementia. The level of agreement between experts in the field of dementia concerning cortical, subcortical and frontal dementia was established. Nowadays these syndromes are implemented in clinical practice; the discussion about the validity and reliability of these concepts however has diminished. Forty-one national and international dementia experts of four disciplines completed a questionnaire, based on the cognitive section of the CAMDEXR. For each syndrome they marked whether the cognitive function mentioned was impaired or unimpaired in cortical, subcortical and frontal dementia. The level of agreement between experts was determined by use of a derivative of the kappa-coefficient. Cortical dementia was characterised by high levels of agreement between the experts. With an observed level of agreement of 0.76, experts reached the highest consensus about this syndrome. Less agreement was observed in the judgements of subcortical and frontal dementia, with observed levels of agreement of 0.64 and 0.67 respectively. No differences were found in the assessments of national and international experts, as well as between the participating disciplines. Apparently, the application of these syndromes in clinical practice is difficult. Because of this confusion the practical meaning is limited, and one may wonder wether these concepts must still be used in clinical practice.

CAMDEX, can it be more efficient? Observational study on the contribution of four screening measures to the diagnosis of dementia by a memory clinic team.

OBJECTIVE: To evaluate the efficiency of the CAMDEX by exploring the contribution of its four main screening measures to the diagnosis of dementia at a memory clinic. METHODS: A retrospective descriptive study was conducted on the diagnostic practice in a memory clinic regarding all consecutively referred patients who came for a first assessment. A standardised examination based on the CAMDEX included three cognitive tests (CAMCOG, MMSE, IMCT) and a test for functional competence (BDS). The predictive value of the tests was estimated by uni- and multivariate analysis with the clinical dementia diagnosis (yes/no) as dependent variable, taking into account the patients' age, education, gender and sensory ability. RESULTS: Of the 180 patients consecutively referred, 150 completed the assessments and entered the study. Multivariate analysis revealed that the CAMCOG-score contributed most to the clinical diagnosis and was consistent with 84% of the clinical diagnoses using the conventional cutoff 79/80. The CAMCOG-score correlated best with the clinical diagnosis, however, at a cutoff score of 81/82. Forty-one patients (27%) scored closely around (+/-5 points) the CAMCOG cutoff of 79/80. In this group 19 of the total of 23 deviations from the CAMCOG cutoff (83%) occurred. The patients' age, education, gender and visual ability explained some cases where the team's diagnosis deviated from the conventional cutoff score. CONCLUSION: Among four screening measures, after control, the CAMCOG was the only significant predictor for the clinical diagnosis of dementia. To gain efficiency, the screening measures of the CAMDEX protocol may be restricted to the CAMCOG. The interpretation of CAMCOG-scores around the cut-off is problematic. This indicates the need for reference values.

Cognitive performance in relation to MRI temporal lobe volume in schizophrenic patients and healthy control subjects.

The aim of this study was to identify whether specific deficits in cognitive processing are present in schizophrenia and whether these are related to the volume of temporal and limbic structures. Twenty-seven schizophrenic outpatients were compared with 19 matched control subjects. Compared with control subjects, patients performed complex tasks disproportionately worse than they performed simple tasks. No group differences were found with regard to temporal and limbic volume. Volume of the parahippocampal gyrus was correlated with cognitive performance. The findings are interpreted as evidence for a dysfunction in the maintenance of task-relevant information and the inhibition of irrelevant information.

Cognitive dysfunctions and white matter lesions in patients with bipolar disorder in remission.

OBJECTIVE: To compare cognitive functioning in relation to white matter lesions in bipolar disorder in remission and schizophrenia. METHOD: Cognitive performance and the occurrence of white matter lesions on MRI images of the brain were assessed in 22 patients with bipolar disorder in remission, 22 patients with schizophrenia and 22 healthy volunteers. RESULTS: Performance of tests of memory, speed and cognitive flexibility was significantly impaired in both patient groups. The frequency of white matter lesions did not differ significantly between the three groups. No differences in cognitive performance were found between patients with white matter lesions and patients without such lesions. CONCLUSION: White matter lesions apparently do not underlie cognitive deficits that are found in patients with bipolar disorder in remission and in patients with schizophrenia.

Normal cognitive performance in patients with chronic alcoholism in contrast to patients with Korsakoff's syndrome.

This study investigated which cognitive deficits are associated with chronic alcoholism. Neuropsychological profiles and MRI brain structure volumes of 14 patients with Korsakoff's syndrome, 15 patients with chronic alcoholism, and 16 healthy control subjects were compared. The patients with alcoholism had a normal cognitive performance and normal brain structure volumes. The patients with Korsakoff's syndrome had performance deficits on tests of memory, visuoperceptual, and executive functions, as well as reduced brain structure volumes. The results suggest that the cognitive deficits cannot be ascribed to mere chronic consumption of alcohol. If cognitive deficits are present in patients with chronic alcoholism, this may point to an underlying brain disorder.

The behavioural assessment of the dysexecutive syndrome as a tool to assess executive functions in schizophrenia.

Recent research into the cognitive dysfunctions in schizophrenia has focused on executive deficits. This study investigates performance of patients with schizophrenia on the recently developed Behavourial Assessment of the Dysexecutive Syndrome (BADS). Matched groups of 24 patients with schizophrenia and 17 healthy volunteers were administered the BADS, the Modified Card Sorting Test (MCST), the Tower of London (TOL), a test of general intelligence, and measures of daily functioning. Performance of the schizophrenic group was significantly below that of the control group on the BADS and the MCST, but not on the TOL. The BADS correlated weakly with the MCST. Both tests showed a modest correlation with daily functioning. The BADS appears to offer a useful contribution to the assessment of executive deficits in schizophrenia.

The interview for deterioration in daily living activities in dementia: agreement between primary and secondary caregivers.

Inability to perform activities of daily life is inherent to dementia and an essential component of its severity. Examination of this disability is crucial for diagnosis, management of the patient and family, and evaluation of treatment effects. To examine everyday disability in community-dwelling patients with mild dementia, we developed the Interview for Deterioration in Daily living Activities in Dementia (IDDD) at the memory clinic of the Academic Medical Center at Amsterdam. The IDDD is a caregiver-based measure, which consists of 20 concretely worded items, reflecting the initiative to perform and actual performance of self-care and more complex activities. The original version of the IDDD (1988) was an interview measure, but since 1990 a paper-and-pencil version has been used, which has good construct validity and test-retest reliability, as well as good responsiveness to deterioration over 6 months. In the present study, we examined interobserver agreement among 25 caregiver pairs, which consisted of primary and secondary caregivers. Although the reliability of caregiver reports is often questioned, we found substantial to almost perfect agreement at subscale level and acceptable agreement for most of the items. We conclude that the paper-and-pencil version of the IDDD is a suitable instrument for the description and discrimination of disability among patients with mild dementia still living at home. The IDDD may also be a useful method to incorporate in clinical trials and longitudinal studies.

Feasibility of cognitive screening of patients with ischaemic stroke using the CAMCOG. A hospital-based study.

Brief screening tests would be convenient for the measurement of cognitive impairment in stroke patients. In these patients aphasia can interfere with test procedures. To evaluate the feasibility of examining cognitive functions in stroke patients we examined 129 patients with an ischaemic stroke using the CAMCOG, a standardised neuropsychological screening test, after an interval of at least 3 months. Most patients (88%) were able to complete the CAMCOG. Patients with severe aphasia were significantly more likely to have an abnormal CAMCOG score than patients without aphasia [relative risk (RR) 4.0, 95% confidence interval (CI) 2.8-5.8]. The group of patients with moderate aphasia was not at higher risk of having an abnormal CAMCOG score than patients without aphasia (RR 1.4, 95% CI 0.6-2.8). Looking for other factors that might correlate with the scores, logistic regression analysis revealed age as the only significant factor for the prediction of the CAMCOG score (odds ratio 4.0, 95% CI 1.2-13.2). We concluded that the CAMCOG can conveniently be used for screening cognitive functions in patients with cerebral infarcts, even if there is moderate aphasia.

Are white matter lesions directly associated with cognitive impairment in patients with lacunar infarcts?

Forty-four patients (mean age 66, SD 8 years) with either clinical evidence of a focal lacunar syndrome (n = 36) or with disorders of memory or gait (n = 8) in the presence of a lacunar infarct on CT were studied for cognitive functioning and for the presence of white matter lesions on MRI. MR images were assessed by a neurologist and a neuroradiologist blinded to the clinical data. Thirty-six patients had one or more lacunar infarcts on CT or MRI (in the thalamus in 5, in the caudate nucleus in 3 and in the internal capsule or corona radiata in the remaining patients). Twelve patients had multiple infarcts. Severe lesions of the white matter were found in 13 patients, mild to moderate lesions in 20 patients. Scores on Digit Span, Digit Symbol and delayed recall of the 15-Words test were significantly lower in group with severe lesions, whilst there was a trend in the same direction for the Cognitive part of the Cambridge Examination of Mental Disorders in the Elderly, the Trailmaking B, Stroop colour interference test and the delayed visual reproduction of the Wechsler Memory Scale. These findings suggest that diffuse lesions of the white matter are an independent factor in the pathogenesis of intellectual dysfunction, also in patients with lacunar infarcts, but a truly independent analysis is difficult because the most severe involvement of the white matter tended to be associated with the largest number of lacunar infarcts.

Presentation and course of AIDS dementia complex: 10 years of follow-up in Amsterdam, The Netherlands.

OBJECTIVE: To assess the clinical presentation and course of the AIDS dementia complex (ADC). DESIGN: Retrospective study of a consecutive series of symptomatic HIV-1-infected patients [Centers for Disease Control and Prevention (CDC) stages IVA, B, C and D] evaluated for neurological symptoms between 1982 and 1992. SETTING: An academic referral centre for AIDS. PATIENTS: A total of 536 symptomatic HIV-1-infected patients evaluated for neurological symptoms between 1982 and 1992. INTERVENTIONS: Zidovudine treatment, which was introduced in The Netherlands on 1 May 1987 for patients with severe symptoms of HIV infection (CDC stages IVA, B, C and D). MAIN OUTCOME MEASURES: Diagnosis of ADC and CD4 cell count, clinical features, neuropsychological abnormalities, computed tomography (CT) and magnetic resonance imaging (MRI) abnormalities, cerebrospinal fluid (CSF) findings and course in patients with ADC. RESULTS: ADC was diagnosed in 40 out of 536 (7.5%) immunosuppressed, neurologically symptomatic HIV-1-infected patients in CDC stage IV, and was the AIDS-defining illness in six. The mean CD4 cell count of the 40 patients with ADC was 109 x 10(6)/l. Neuropsychological abnormalities in 15 out of 17 patients tested were in accordance with subcortical dementia. On CT scan of the brain, 70% showed no or only mild cortical atrophy. MRI was more sensitive than CT scan for detecting white matter abnormalities (73 versus 35%; P = 0.02). CSF examination showed mononuclear pleocytosis in 25%, protein level increase in 55%, and HIV-1 p24 core protein in 38% (13 out of 34). The mean survival was 6.7 months in the 40 ADC patients, but 4 months in 20 patients who had never used zidovudine, compared with 14.8 months in 10 patients who started zidovudine after they were classified as having ADC (P < 0.001). Three of these 10 patients improved remarkably, and two slightly, after starting zidovudine. ADC developed after discontinuation of zidovudine in nine patients. Only one patient developed ADC while receiving 600 mg zidovudine. CONCLUSIONS: MRI is more sensitive than CT for detecting white matter abnormalities. To date, there is no specific or sensitive CSF marker for ADC. Zidovudine may improve symptoms and prolong survival in patients with ADC, which rarely developed with continued zidovudine use in our study.

[An outpatient clinic for memory disorders; initial experiences]. / Een polikliniek voor geheugenstoornissen; eerste ervaringen.

The department of neurology of the Academisch Medisch Centrum started an outpatient memory clinic in 1987 for patients aged 65 and older. Its specific aims are: assessment of elderly patients with memory problems, treatment where appropriate, and advice; clinical research; teaching and training. The clinic has run full-time since 1990. The approach is multidisciplinary. We describe our findings in the first 75 patients who were referred by their general practitioners because of forgetfulness or possible dementia: 72 of them had a complete investigation; 30 patients were not demented; three could be reassured because their performance was within normal limits. Four patients were depressed and they improved on therapy. Forty-two patients were demented. All had a CT scan and comprehensive blood tests but a curable cause for the dementia syndrome was never identified. This result was expected on account of the probably low frequency of 'reversible' causes and patient selection. Secondary prevention was important when a vascular component contributed to the pathogenesis of the mental deterioration (n = 6). Even when no curable condition was found, clarity about diagnosis and prognosis was important not only to the relatives but also to the general practitioner in planning the future management of the patient. Fifty-five of the 72 patients were older than 65 years which means that we do see the patients we are particularly interested in. The clinic offers facilities for clinical research. In the project 'Diagnostiek bij dementiesyndroom' (Diagnostics in dementia syndrome) we investigate the utility of ancillary investigations in relation to the outcome in demented patients.

Hypertension in the elderly is associated with white matter lesions and cognitive decline.

Forty-two elderly patients (mean age, 66.2 +/- 5.1 yr) with hypertension, treated for an average of 17.3 years (standard deviation, 10.3), and 42 control subjects (mean age, 66.5 +/- 4.8 yr), matched for age, sex, and level of education, were studied with regard to the detection of lesions in the cerebral white matter with magnetic resonance imaging (MRI), particularly with axial T2-weighted images. The assessment of the MRI scans was blinded. Ten hypertensive patients showed confluent lesions in the white matter, versus only 1 control subject (Chi-square test, p = 0.01). The presence of diffuse lesions of the white matter was related to age but not to the known duration of hypertension, nor to the presence of any other cardiovascular risk factors. Cognitive function was measured in 34 hypertensive patients and in 18 control subjects. Results of the Mini-Mental State Examination, the Stroop color-word test, Trailmaking test, and the visual subtest of the Wechsler Memory Scale were worse in patients with confluent lesions of the white matter; there was no difference in mental functioning between hypertensive patients and control subjects with normal white matter or with only small focal lesions. Our findings suggest that long-standing hypertension in some patients may cause not only strokes but also chronic end-organ damage of the brain in the form of demyelination of the white matter, with cognitive decline.

[CAMDEX-N: the Dutch version of the Cambridge Examination for Mental Disorders of the Elderly with automatic data processing]. / CAMDEX-N: de Nederlandse versie van de Cambridge Examination for Mental Disorders of the Elderly met geautomatiseerde dataverwerking.

In the study of dementia four distinct categories of instruments can be distinguished: instruments to examine cognitive dysfunction, to measure the severity of dementia, to assess disturbances in daily behaviour, and instruments to make a differential diagnosis of dementia. The Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), published in 1988, incorporates these four categories in a single comprehensive interview schedule. Items related to the diagnosis of clouded/delirious state, depression and other psychiatric symptoms are also included. The Dutch version (CAMDEX-N) and accompanying software for data analysis and for scientific research were developed. Items were added to the section on physical and neurological examination, and to the section on ancillary investigations. The software can be adapted to future developments in dementia research.

[Measurement of activities of daily living in patients with dementia living at home: development of a questionnaire]. / Meten van het dagelijks functioneren van thuiswonende dementiepatiënten: ontwikkeling van een vragenlijst.

In clinical practice and for scientific research a method is needed for the assessment of changes in functioning in daily life of dementia patients living at home. As existing methods have their limitations, a questionnaire was developed (the Interview for Deterioration in Daily life in Dementia: IDDD), to be answered by caregivers. The questionnaire concerns self-care and complex activities, that are usually performed by men as well as women. Attention is paid to the difference between lack of initiative and impaired performance itself. Caregivers are interviewed in a structured interview. A study among 30 caregivers of dementia patients living at home, showed the relevance and usefulness of the questions. The questionnaire shows high internal consistency, which may be the result of our structured interview technique.

Assessing the severity of dementia. Patient and caregiver.

In dementia there is cognitive impairment, disability in daily life, and sometimes behavioral disturbance. These changes are a burden for the caregivers of patients with dementia. Few studies are available that examine all these aspects and their interrelationships in a single patient group. In our study we selected detailed methods for assessment of all these aspects. Interrelationships were studied in 30 mild to moderately impaired patients with dementia and their caregivers. Although the relations of cognitive deterioration to disability in daily life and of burden experienced by the caregiver to patient's condition were stronger than often reported, it was impossible to deduce the overall severity of dementia from one single aspect. Thus, for effective management of patients and caregivers, for evaluation of individual treatment or of clinical trials, attention should be paid to all the different aspects of patients' condition and caregivers' burden. Outcome measurements will then be more valid.

SPECT in the diagnosis of Alzheimer's disease and multi-infarct-dementia.

SPECT with Tc-99m HM-PAO as a radiopharmaceutical was performed in 17 patients meeting research criteria for Alzheimer's disease (AD), in 10 patients with a clinical diagnosis of multi-infarct-dementia (MID) and in 12 healthy volunteers. Regional tracer uptake was measured in frontal, parietal, and temporoparietal regions. A statistically significant decrease of tracer uptake in the temporoparietal region was found in AD-patients compared with controls. AD-patients showed less activity in this region than MID-patients, but this difference did not reach statistical significance. In both AD- and MID-patients decrease of tracer uptake was not correlated with dementia severity. We conclude that SPECT brain imaging is not yet ready for routine use in the distinction between AD and MID.